Abstract
In order to produce proteins essential for their propagation, many pathogenic human viruses, including SARS-CoV-2, the causative agent of COVID-19 respiratory disease, commandeer host biosynthetic machineries and mechanisms. Three major structural proteins, the spike, envelope and membrane proteins, are amongst several SARS-CoV-2 components synthesised at the endoplasmic reticulum(ER) of infected human cells prior to the assemblyof newviral particles. Hence, the inhibition of membrane protein synthesis at the ER is an attractive strategy for reducing the pathogenicity of SARSCoV- 2 and other obligate viral pathogens. Using an in vitro system, we demonstrate that the small molecule inhibitor ipomoeassin F (Ipom-F) potently blocks the Sec61-mediated ER membrane translocation and/ or insertion of three therapeutic protein targets for SARS-CoV-2 infection; the viral spike and ORF8 proteins together with angiotensinconverting enzyme 2, the host cell plasma membrane receptor. Our findings highlight the potential for using ER protein translocation inhibitors such as Ipom-F as host-targeting, broad-spectrum antiviral agents.
| Original language | English |
|---|---|
| Article number | jcs257758 |
| Journal | Journal of Cell Science |
| Volume | 134 |
| Issue number | 4 |
| ISSN | 0021-9533 |
| DOIs | |
| Publication status | Published - 19 Feb 2021 |
| Externally published | Yes |
| MoE publication type | A1 Journal article-refereed |
Bibliographical note
Funding Information:This work was supported by a Wellcome Trust Investigator Award in Science 204957/Z/16/Z (S.H.), an AREA grant 2R15GM116032-02A1 from the National Institute of General Medical Sciences of the National Institutes of Health and a Ball State University (BSU) Provost Startup Award (W.Q.S.). Deposited in PMC for immediate release.
Publisher Copyright:
© 2021 Company of Biologists Ltd. All rights reserved.
Fields of Science
- Cell-free translation
- Endoplasmic reticulum
- ER membrane complex
- Sec61 translocon
- Viral protein biogenesis